A fully synthetic self-adjuvanting globo H-Based vaccine elicited strong T cell-mediated antitumor immunity
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Authors: | Zhifang Zhou Guochao Liao Satadru S Mandal Sharad Suryawanshi Zhongwu Guo |
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Institution: | a Department of Chemistry , Wayne State University , 1501 Cass Avenue , Detroit , Michigan 48202 , USA . Email: ; Tel: +1-313-577-2557 |
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Abstract: | Therapeutic cancer vaccines based on the abnormal glycans expressed on cancer cells, such as the globo H antigen, have witnessed great progress in recent years. For example, the keyhole limpet hemocyanin (KLH) conjugate of globo H has been on clinical trials as a cancer vaccine. However, such vaccines have intrinsic problems, such as inconsistence in eliciting T cell-mediated immunity in cancer patients and difficult quality control. To address the issue, a structurally defined fully synthetic glycoconjugate vaccine composed of globo H and monophosphoryl lipid A (MPLA) was developed. The new vaccine was shown to elicit robust IgG1 antibody responses and T cell-dependent immunity, which is desired for anticancer vaccines, and induce significantly faster and stronger immune responses than the globo H–KLH conjugate. Moreover, it was self-adjuvanting, namely, inducing immune responses without the use of an external adjuvant, thus MPLA was not only a vaccine carrier but also a build-in adjuvant. It was also found that antibodies induced by the new vaccine could selectively bind to and mediate strong complement-dependent cytotoxicity to globo H-expressing MCF-7 cancer cell. All of the results have demonstrated that the globo H–MPLA conjugate is a better cancer vaccine than the globo H–KLH conjugate under experimental conditions and is worth further investigation and development. |
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